Total marrow irradiation: a new ablative regimen as part of tandem autologous stem cell transplantation for patients with multiple myeloma

Abstract

Purpose: To establish feasibility, maximum tolerated dose (MTD), and potential efficacy of ablative dose total marrow irradiation (TMI) delivered by helical tomotherapy in patients with multiple myeloma (MM).

Experimental design: Patients with responding or stable MM received tandem autologous stem cell transplants, first with melphalan 200 mg/m(2), and 60 days or later with TMI. TMI doses were to be escalated from 1,000 cGy by increments of 200 cGy. All patients received thalidomide and dexamethasone maintenance.

Results: Twenty-two of 25 enrolled patients (79%) received tandem autologous stem cell transplantation (TASCT): TMI was administered at a median of 63.5 days (44-119) after melphalan. Dose-limiting toxicities at level 5 (1,800 cGy) included reversible grade 3 pneumonitis, congestive heart failure, and enteritis (1), and grade 3 hypotension (1). The estimated median radiation dose to normal organs was 11% to 81% of the prescribed marrow dose. Late toxicities included reversible enteritis (1), and lower extremity deep venous thrombosis during maintenance therapy (2). The complete and very good partial response rates were 55% and 27% following TASCT and maintenance therapy. At a median of 35 months of follow-up (21-50+ months), progression-free and overall survival for all patients were 49% (95% CI, 0.27-0.71) and 82% (0.67-1.00).

Conclusion: Ablative dose TMI as part of TASCT is feasible, and the complete response rate is encouraging. Careful monitoring of late toxicities is needed. Further assessment of this modality is justified at the 1,600 cGy MTD level in MM patients who are candidates for ASCT.

Conflict of interest statement

Conflict-of interest disclosure: Jeffrey Wong M.D. is the recipient of a research grant from Tomotherapy Hi-Art System, Madison, WI. The other authors declare no competing conflicts of interests

©2010 AACR.

Figures

Figure 1

Treatment Plan Dose Distribution Color Wash From a Patient treated With 1600 cGy of TMI

Figure 2

Median Organ Doses with TMI. Median (D50) dose for each organ compartment is shown. Bar graphs represent an average of the dose for the 3-6 patients at each TMI dose level.

Figures 3

Kaplan-Meier Estimates of Progression-Free and Overall Survival for All 25 Patients Treated by Intent to Treat Analysis